Dutch court blocks Merck’s injectable Keytruda in eight countries over Halozyme patent

The Hague District Court found that Merck’s subcutaneous cancer treatment infringes a patent covering modified hyaluronidase technology, highlighting the reach of drug-delivery patents and the potential for cross-border enforcement.

A Dutch court has ordered Merck Sharp & Dohme to stop manufacturing and selling its subcutaneous formulation of Keytruda in eight European countries after finding that the product infringes a patent owned by Halozyme.

In a judgment dated October 7, 2026, the District Court of The Hague rejected Merck’s challenge to the validity of European patent EP 2 797 622 and ruled that Keytruda SC falls within the scope of the patent’s claims.

The injunction covers Belgium, Denmark, France, Ireland, Italy, the Netherlands, Sweden, and Switzerland. Merck must comply within seven days after formal service of the judgment. The cross-border relief is conditional on the continued validity of the relevant national patent rights.

The decision, Merck Sharp & Dohme BV v. Halozyme Inc., ECLI:NL:RBDHA:2026:29643, represents a significant setback for Merck’s plans to expand access to Keytruda through an injection under the skin rather than an intravenous infusion.

Patent dispute centers on drug-delivery technology

Keytruda, whose active ingredient is pembrolizumab, is an immunotherapy used to treat several forms of cancer. Its traditional formulation is administered intravenously, while Keytruda SC is designed for subcutaneous administration.

The subcutaneous formulation contains berahyaluronidase alfa, also known as ALT-B4, an enzyme developed by South Korean biotechnology company Alteogen. Merck purchases the enzyme from Alteogen for use in Keytruda SC.

Hyaluronidase enzymes temporarily increase tissue permeability, helping medicines that would otherwise require intravenous administration to be delivered under the skin.

Halozyme develops and licenses drug-delivery technologies based on recombinant human PH20 hyaluronidase. Its technologies have enabled the subcutaneous delivery of certain biologic medicines, including Bristol Myers Squibb’s Opdivo SC, which is marketed in Europe under license from Halozyme.

The patent at the center of the dispute, EP 2 797 622, is titled PH20 Polypeptide Variants, Formulations and Uses Thereof. It covers modified PH20 polypeptides with specified amino acid substitutions that exhibit increased stability in the presence of phenolic preservatives.

Although Keytruda SC does not contain a phenolic preservative, the court found that ALT-B4 itself met the patent’s functional stability requirement. It concluded that the absence of a preservative in the finished medicine did not take the enzyme outside the scope of the product claims.

Court rejects Merck’s validity challenge

Merck sought a declaration that Keytruda SC did not infringe the Dutch part of the patent and requested that the patent be invalidated in the Netherlands.

Its arguments challenged the patent’s sufficiency of disclosure, alleged added subject matter, novelty, and inventive step. Merck also argued that its formulation, which uses ALT-B4 rather than Halozyme’s own enzyme, did not fall within the patent’s claims. The court rejected the invalidity arguments, finding that the patent was sufficiently disclosed, novel, inventive, and free from impermissible added subject matter.

In assessing infringement, the court considered the structure and characteristics of ALT-B4. It found that the enzyme contained amino acid substitutions at positions identified in the patent and that testing supported Halozyme’s position that ALT-B4 had increased stability in the presence of phenolic preservatives compared with unmodified PH20.

Merck argued that Keytruda SC did not use the claimed technical effect because the formulation contained no phenolic preservative. The court rejected this argument, reasoning that the patent claimed a product defined partly by functional characteristics. It was therefore not necessary for the finished medicine to contain a phenolic preservative or to make practical use of the enzyme’s increased stability in its presence.

The court consequently dismissed Merck’s claims and upheld Halozyme’s counterclaim for infringement.

Cross-border injunction covers eight national patent rights

The court prohibited Merck from infringing the Belgian, Danish, French, Irish, Italian, Dutch, Swedish, and Swiss national parts of EP 2 797 622.

The prohibited activities include manufacturing, commissioning the manufacture of, offering, marketing, using, importing, or stocking Keytruda SC for those purposes in the covered countries.

The court also prohibited Merck from unlawfully facilitating infringement by other companies within its group in Belgium, Denmark, France, Ireland, and Italy. This includes authorizing or facilitating infringement through the availability or use of its European marketing authorization for Keytruda SC.

The injunction is backed by a penalty of €25,000 per day of noncompliance or, at Halozyme’s choice, €25,000 per affected product, subject to a total cap of €50 million.

The ruling is notable for its approach to cross-border patent enforcement. The court considered whether it had jurisdiction to determine infringement of the relevant foreign national patent rights and whether the proceedings should be suspended pending separate validity challenges in other countries.

It concluded that there was no sufficiently substantial likelihood that the relevant foreign patent rights would be invalidated to justify suspending the case. The court therefore granted the injunction, subject to conditions tied to the outcome of national validity proceedings.

If a relevant national part of the patent is subsequently invalidated, the injunction relating to that right will cease to operate. It may revive if a later appeal or cassation decision restores the patent’s validity.

The decision does not amount to a final determination by each national court of the validity of its respective patent right.

Implications for pharmaceutical patent strategy

The dispute illustrates the importance of patents covering formulation and drug-delivery technologies, rather than only those directed to a medicine’s active pharmaceutical ingredient.

Changing a medicine from intravenous to subcutaneous administration can offer practical advantages for patients and health care providers. However, developing an alternative delivery method may still depend on biological components protected by third-party patents.

The ruling is particularly relevant to freedom-to-operate assessments. Merck’s use of an enzyme developed by Alteogen did not, in the court’s assessment, place Keytruda SC outside the scope of Halozyme’s patent claims. The judgment also shows how a patent’s functional language can matter when assessing whether a competing product falls within its protection, even when the finished formulation does not use the precise technical effect in question.

For patent owners, the case demonstrates the potential reach of cross-border remedies where the court has jurisdiction and the relevant national rights support relief. However, the conditional nature of the injunction also underscores that national validity proceedings remain important.

The decision comes as Merck seeks to expand the ways in which Keytruda can be administered. The injunction concerns Keytruda SC, not the established intravenous formulation, which is outside the scope of this patent ruling.

Wider dispute remains ongoing

The Dutch proceedings form part of Halozyme’s broader enforcement efforts concerning its drug-delivery patent portfolio. Halozyme previously obtained a preliminary injunction in Germany concerning Keytruda SC. Merck has also faced patent litigation in the United States over its subcutaneous pembrolizumab formulation, marketed there as QLEX.

The Dutch judgment gives Halozyme a significant victory in Europe, but the wider disputes over the scope and validity of its patents remain subject to proceedings in other jurisdictions.

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